Treatment of proteinuria

Abstract

Provided is a composition comprising a phenyl pyrrole aminoguanidine derivative for use in a method of treating kidney disease, such as nephrotic syndromes.

1 . A method of treating membranous nephropathy in a human comprising orally administering to the human about 50-200 mg daily of (E)-N-trans-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidium acetate (AP1189), or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the membranous nephropathy is idiopathic membranous nephropathy (iMN). 
     
     
         3 . The method of  claim 1 , wherein the AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof, is administered once daily. 
     
     
         4 . The method of  claim 1 , wherein the human is anti-PLA2-Receptor positive. 
     
     
         5 . The method of  claim 1 , wherein the human has a U-protein/creatinine ratio >3.5 g/g, prior to the administration. 
     
     
         6 . The method of  claim 1 , wherein the human has a U-albumin/creatinine ratio >2.2 g/g, prior to the administration. 
     
     
         7 . The method of  claim 1 , wherein the human has a eGFR>30 ml/min/1.73m 2 , prior to the administration. 
     
     
         8 . The method of  claim 1 , wherein the human is being treated with an ACE-inhibitor and the ACE-inhibitor is administered concurrently with the AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 1 , wherein the human is being treated with an angiotensin II receptor blocker and the angiotensin II receptor blocker is administered concurrently with the AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , further comprising administration to the human of an ACE inhibitor. 
     
     
         11 . The method of  claim 1 , further comprising administration to the human of an angiotensin II receptor blocker. 
     
     
         12 . The method of  claim 1 , wherein the human is administered 50 mg daily of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 1 , wherein the human is administered 100 mg daily of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 1 , wherein the human's urinary protein excretion is decreased after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof, as compared to the human's urinary protein excretion prior to the daily administration. 
     
     
         15 . The method of  claim 1 , wherein the human's urinary albumin excretion is decreased after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof, as compared to the human's urinary albumin excretion prior to the daily administration. 
     
     
         16 . The method of  claim 1 , wherein the human's fractional urine excretion of albumin (FEAlb) is decreased after 4 weeks of daily administration of AP1189 or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof, as compared to the human's FEAlb prior to the daily administration. 
     
     
         17 . The method of  claim 1 , wherein the human's plasma albumin is decreased after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof, as compared to the human's plasma albumin prior to the daily administration. 
     
     
         18 . The method of  claim 1 , wherein the human's urinary protein excretion is <0.3 g/d accompanied by a normal P-albumin concentration, and a normal P-creatinine value after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 1 , wherein the human's urinary protein excretion is <0.3 g/d and a 50% or greater reduction from peak values accompanied by an improvement or normalization of the human's P-albumin concentration, and stable O-creatinine value, after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 1 , wherein the human's eGFR calculated from both P-creatinine and P-cystatin C is decreased, after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 1 , wherein the human's urinary creatinine clearance (Ccr) is decreased, after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 1 , wherein the human's cholesterol is decreased, after 4 weeks of daily administration of AP1189, or the tautomeric form thereof, or the pharmaceutically acceptable salt thereof. 
     
     
         23 . A method of treating membranous nephropathy in a human comprising administering a dosage form comprising
 (E)-N-trans-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidium acetate (AP1189), or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, and   an angiotensin II receptor blocker.   
     
     
         24 . A method of treating membranous nephropathy in a human comprising administering a dosage form comprising
 (E)-N-trans-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidium acetate (AP1189), or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, and   an ACE inhibitor.